Effects of Intranasal Fluticasone Plus Azelastine on Airway Inflammation in Patients With Asthma & Allergic Rhinitis (MAN06)

April 4, 2019 updated by: University of Dundee

Proof of Concept Study to Assess Downstream Effects of Using Combined Intranasal Fluticasone Propionate Plus Azelastine Nasal Spray on Asthmatic Inflammation in Patients With Persistent Asthma and Allergic Rhinitis

Single centre, double-blind, placebo controlled, adaptive design, cross-over trial. The primary objective is to assess the additive effects of using combined intranasal fluticasone propionate plus azelastine nasal spray on airway hyperresponsiveness. This is in patients with persistent asthma and allergic rhinitis, receiving inhaled steroid.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The unified allergic airway describes patients who have both asthma and allergic rhinitis. Both conditions have similar underlying pathophysiology in terms of T-helper 2 (Th2) cell activation. Patients with unified allergic airway disease have a greater burden in terms of impaired quality of life, and the presence of airway hyper-responsiveness (AHR) to methacholine is a hallmark of their underlying asthmatic inflammatory process. Targeting the Th2 allergic airway with a topical antihistamine may improve airway hyperresponsiveness.

It has previously been shown that in patients with unified allergic airway disease, using inhaled fluticasone alone (100 micrograms per day) produced a 1.2 doubling dilution (dd) shift in the provocative concentration of methacholine required to reduce forced expiratory volume (FEV1) by 20% (PC20). However when adding nasal fluticasone to the inhaled steroid, there was a 1.79 dd shift. This difference (0.58 dd, 95% CI 0.78, 1.95) was not statistically significant. However the combined treatment did result in significant improvement in rhinitis quality of life, nasal inflammation and inspiratory flow.

The investigators will repeat this previous concept, but compare intranasal fluticasone with azelastine (an antihistamine) nasal spray versus placebo nasal spray, in atopic asthmatic patients on inhaled steroid. This will be to assess effects on methacholine PC20, the primary outcome, and to assess the effects on the following secondary outcomes: Exhaled nitric oxide (FeNO), FEV1, morning peak expiratory flow (PEF), impulse oscillometry, peak nasal inspiratory flow (PNIF), nasal nitric oxide (NO), blood eosinophils, eosinophilic cationic protein (ECP), nasal symptoms, asthma control and quality of life; and rhinitis quality of life.

Twenty adults 18 and up, with allergic asthma will be enrolled. They will have a run-in on 2 weeks of 200 micrograms beclometasone inhaler and then be randomised to add either intranasal fluticasone and azelastine, or placebo nasal spray to their treatment (double blind). Treatment period one will be 3-5 weeks followed by a washout of 2-4 weeks, and crossover to treatment period two for 3-5 weeks. Due to the crossover nature of this study participants will receive both treatments in random order. There will be an Interim analysis after 20 participants complete the study per protocol and the exact required sample size will be recalculated (Pocock/adaptive design).

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Scotland
      • Dundee, Scotland, United Kingdom, DD1 9SY
        • Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female volunteers, aged 18 years and above, with persistent asthma and allergic rhinitis
  • On a minimum of 200μg BDP of Inhaled corticosteroid (ICS)
  • FEV1 ≥ 60 % predicted
  • Positive skin prick test, or record of elevated allergen-specific IgE to at least 1 perennial allergen
  • Methacholine PC20 < 8mg/ml at Visit 1
  • Ability to give informed consent

Exclusion Criteria:

  • Other respiratory diseases such as COPD, bronchiectasis or allergic bronchopulmonary aspergillosis (ABPA) which are considered to be significant in the opinion of the study physician Nasal polyps ≥ Grade 2
  • An asthma exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month of the study commencement, or 3 months if hospital admission was required
  • Any clinically significant medical condition that may endanger the health or safety of the participant. For example: Patients who have tuberculosis or any type of untreated infection or have had recent surgical operation or injury to the nose or mouth.
  • Participation in another trial within 30 days before the commencement of the study
  • Pregnancy or lactation
  • Unable to comply with the procedures of the protocol
  • Unable or unwilling to consent
  • Taking prohibited medications as listed in section 6.7.2 Prohibited Medications
  • Hypersensitivity to the active substances or to any of the excipients of Dymista Nasal Spray.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Azelastine-Fluticasone Nasal
137 micrograms azelastine hydrochloride / 50 micrograms fluticasone propionate per actuation. 1 squirt twice daily
Drug: Azelastine-Fluticasone Nasal
137 micrograms azelastine hydrochloride / 50 micrograms fluticasone propionate
Other Names:
  • Dymista
Placebo Comparator: Placebos
contains the same components as Dymista nasal spray with the exception of the active ingredients. 1 squirt twice daily.
Drug: Placebos
Placebo nasal spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Methacholine PC20
Time Frame: 3-5 weeks
The provocative concentration of methacholine required to produce a 20% drop (PC20) in forced expiratory volume in 1 second (FEV1)
3-5 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exhaled nitric oxide (FeNO)
Time Frame: 3-5 weeks
A measurement of the amount of inflammation in the airways
3-5 weeks
Forced expiratory volume in 1 second (FEV1)
Time Frame: 3-5 weeks
The amount of air exhaled in the first second of a forced expiration.
3-5 weeks
Morning peak expiratory flow (PEF)
Time Frame: 3-5 weeks
A measurement of how quickly a patient can blow air out of their lungs
3-5 weeks
Airway resistance at 5Hz (R5)
Time Frame: 3-5 weeks
A measurement of the total airway resistance at the frequency of 5 Hertz
3-5 weeks
Airway resistance at 20Hz (R20)
Time Frame: 3-5 weeks
A measurement of the proximal airways resistance at the frequency of 20 Hertz
3-5 weeks
Peripheral airway resistance (R5-R20)
Time Frame: 3-5 weeks
A measurement of the peripheral airway resistance by taking the resistance at 5Hz and subtracting the resistance at 20 Hertz
3-5 weeks
Airway Reactance (X5)
Time Frame: 3-5 weeks
A measurement of the peripheral capacitive reactance at the frequency of 5 Hertz
3-5 weeks
Airway Reactance area under the curve (AX)
Time Frame: 3-5 weeks
A measurement of the reactance area between the negative reactance trend and zero.
3-5 weeks
Domiciliary peak nasal inspiratory flow (PNIF)
Time Frame: 3-5 weeks
A measurement of how open or blocked the nasal passages are.
3-5 weeks
Nasal nitric oxide (NO)
Time Frame: 3-5 weeks
A measurement of the amount of inflammation in the nasal passages.
3-5 weeks
Blood eosinophils
Time Frame: 3-5 weeks
A measurement of the amount of eosinophils in the blood
3-5 weeks
Eosinophilic cationic protein (ECP)
Time Frame: 3-5 weeks
A measurement of the amount of Eosinophilic Cationic Protein (ECP) in the blood
3-5 weeks
Total nasal symptom score (TNS4)
Time Frame: 3-5 weeks
A questionnaire to assess four (4) types of nasal symptoms: runny nose, blocked nose, itchy nose, and sneezing.
3-5 weeks
Asthma control questionnaire (ACQ)
Time Frame: 3-5 weeks
A questionnaire to measure the degree of a person's asthma control
3-5 weeks
Asthma quality of life questionnaire (AQLQ)
Time Frame: 3-5 weeks
A questionnaire to measure the functional problems that are most troublesome to adults with asthma.
3-5 weeks
Rhinitis quality of life questionnaire (RQLQ)
Time Frame: 3-5 weeks
A questionnaire to measure the functional problems that are most troublesome to adults with rhinitis.
3-5 weeks
Visual analogue scale (VAS)
Time Frame: 3-5 weeks
a 10 cm line horizontal describing rhinitis symptoms. zero being "not bothersome" and ten being "very bothersome".
3-5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Dundee

Investigators

  • Principal Investigator: Brian Lipworth, MD, Scottish Centre for Respiratory Reseach

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 20, 2017

Primary Completion (Actual)

September 10, 2018

Study Completion (Actual)

September 10, 2018

Study Registration Dates

First Submitted

October 28, 2016

First Submitted That Met QC Criteria

November 1, 2016

First Posted (Estimate)

November 2, 2016

Study Record Updates

Last Update Posted (Actual)

April 8, 2019

Last Update Submitted That Met QC Criteria

April 4, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-001093-17

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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